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- PDB-8h75: FGFR2 in complex with YJ001 -

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Basic information

Entry
Database: PDB / ID: 8h75
TitleFGFR2 in complex with YJ001
ComponentsFibroblast growth factor receptor 2
KeywordsTRANSFERASE / FGFR2 / kinase / YJ001 / complex / inhibitor
Function / homology
Function and homology information


Signaling by FGFR2 amplification mutants / Signaling by FGFR2 fusions / fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell / fibroblast growth factor receptor signaling pathway involved in hemopoiesis / fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow / lateral sprouting from an epithelium / fibroblast growth factor receptor signaling pathway involved in mammary gland specification / mammary gland bud formation / branch elongation involved in salivary gland morphogenesis / mesenchymal cell differentiation involved in lung development ...Signaling by FGFR2 amplification mutants / Signaling by FGFR2 fusions / fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell / fibroblast growth factor receptor signaling pathway involved in hemopoiesis / fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow / lateral sprouting from an epithelium / fibroblast growth factor receptor signaling pathway involved in mammary gland specification / mammary gland bud formation / branch elongation involved in salivary gland morphogenesis / mesenchymal cell differentiation involved in lung development / lacrimal gland development / prostate gland morphogenesis / otic vesicle formation / regulation of smooth muscle cell differentiation / regulation of morphogenesis of a branching structure / orbitofrontal cortex development / squamous basal epithelial stem cell differentiation involved in prostate gland acinus development / embryonic organ morphogenesis / branching morphogenesis of a nerve / endochondral bone growth / morphogenesis of embryonic epithelium / bud elongation involved in lung branching / epidermis morphogenesis / positive regulation of epithelial cell proliferation involved in lung morphogenesis / reproductive structure development / limb bud formation / membranous septum morphogenesis / lung lobe morphogenesis / gland morphogenesis / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / ventricular zone neuroblast division / embryonic digestive tract morphogenesis / mesenchymal cell differentiation / epithelial cell proliferation involved in salivary gland morphogenesis / branching involved in labyrinthine layer morphogenesis / mesenchymal cell proliferation involved in lung development / pyramidal neuron development / branching involved in prostate gland morphogenesis / FGFR2b ligand binding and activation / FGFR2c ligand binding and activation / Activated point mutants of FGFR2 / Phospholipase C-mediated cascade; FGFR2 / regulation of osteoblast proliferation / branching involved in salivary gland morphogenesis / embryonic pattern specification / positive regulation of phospholipase activity / lung-associated mesenchyme development / outflow tract septum morphogenesis / regulation of smoothened signaling pathway / embryonic cranial skeleton morphogenesis / mesodermal cell differentiation / bone morphogenesis / digestive tract development / skeletal system morphogenesis / odontogenesis / positive regulation of mesenchymal cell proliferation / ureteric bud development / inner ear morphogenesis / organ growth / hair follicle morphogenesis / Signaling by FGFR2 IIIa TM / ventricular cardiac muscle tissue morphogenesis / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of osteoblast differentiation / PI-3K cascade:FGFR2 / lung alveolus development / prostate epithelial cord elongation / midbrain development / bone mineralization / fibroblast growth factor binding / positive regulation of cell division / excitatory synapse / PI3K Cascade / positive regulation of Wnt signaling pathway / cell fate commitment / fibroblast growth factor receptor signaling pathway / epithelial to mesenchymal transition / negative regulation of keratinocyte proliferation / embryonic organ development / regulation of ERK1 and ERK2 cascade / SHC-mediated cascade:FGFR2 / positive regulation of cardiac muscle cell proliferation / cellular response to transforming growth factor beta stimulus / cellular response to retinoic acid / FRS-mediated FGFR2 signaling / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of cell cycle / Signaling by FGFR2 in disease / epithelial cell differentiation / axonogenesis / positive regulation of epithelial cell proliferation / post-embryonic development / animal organ morphogenesis / Negative regulation of FGFR2 signaling / lung development / placental growth factor receptor activity / insulin receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity
Similarity search - Function
Fibroblast growth factor receptor family / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. ...Fibroblast growth factor receptor family / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Tinengotinib / Fibroblast growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.75 Å
AuthorsYan, X.E. / Yun, C.H.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: FGFR2 in complex with YJ001
Authors: Yan, X.E. / Yun, C.H.
History
DepositionOct 19, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 25, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 8, 2023Group: Derived calculations / Structure summary / Category: chem_comp / entity / pdbx_entity_nonpoly
Item: _chem_comp.name / _chem_comp.pdbx_synonyms ..._chem_comp.name / _chem_comp.pdbx_synonyms / _entity.pdbx_description / _pdbx_entity_nonpoly.name
Revision 1.2Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Fibroblast growth factor receptor 2
B: Fibroblast growth factor receptor 2
C: Fibroblast growth factor receptor 2
D: Fibroblast growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)144,8119
Polymers143,1974
Non-polymers1,6155
Water46826
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)43.022, 198.595, 67.203
Angle α, β, γ (deg.)90.000, 92.940, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

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Components

#1: Protein
Fibroblast growth factor receptor 2 / FGFR-2 / K-sam / KGFR / Keratinocyte growth factor receptor


Mass: 35799.137 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR2, BEK, KGFR, KSAM / Production host: Escherichia coli (E. coli)
References: UniProt: P21802, receptor protein-tyrosine kinase
#2: Chemical
ChemComp-KX0 / Tinengotinib / 4-[9-(2-chlorophenyl)-6-methyl-2,4,5,8,12-pentazatricyclo[8.4.0.0^{3,7}]tetradeca-1(10),3,6,8,11,13-hexaen-13-yl]morpholine


Mass: 394.857 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C20H19ClN6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: Cl
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 26 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.02 Å3/Da / Density % sol: 39.2 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 0.2M (NH4)2SO4, 0.1M Bis-Tris pH6.0, 25% PEG3350.

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.97915 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 19, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97915 Å / Relative weight: 1
ReflectionResolution: 3.74→50 Å / Num. obs: 16042 / % possible obs: 93.3 % / Redundancy: 6.2 % / Biso Wilson estimate: 49.99 Å2 / Rpim(I) all: 0.092 / Net I/σ(I): 8.3
Reflection shellResolution: 3.74→3.94 Å / Num. unique obs: 803 / Rpim(I) all: 0.346

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Processing

Software
NameVersionClassification
PHENIX1.13_2998refinement
DENZOdata reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1OEC

1oec


Resolution: 3.75→27.8 Å / SU ML: 0.4018 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 24.2147 / Stereochemistry target values: GeoStd + Monomer Library
RfactorNum. reflection% reflection
Rfree0.2377 560 9.74 %
Rwork0.2142 14479 -
obs0.2164 16042 70.59 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 61.72 Å2
Refinement stepCycle: LAST / Resolution: 3.75→27.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8654 0 113 26 8793
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01258955
X-RAY DIFFRACTIONf_angle_d1.777412133
X-RAY DIFFRACTIONf_chiral_restr0.14161346
X-RAY DIFFRACTIONf_plane_restr0.00881539
X-RAY DIFFRACTIONf_dihedral_angle_d25.11323306
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.75-3.870.3112690.2726580X-RAY DIFFRACTION31.29
3.87-4.010.2848470.2275422X-RAY DIFFRACTION45.94
4.01-4.170.24291020.2094966X-RAY DIFFRACTION51.87
4.17-4.360.24831180.18311114X-RAY DIFFRACTION58.22
4.36-4.590.19411270.17911197X-RAY DIFFRACTION64.97
4.59-4.870.22521530.18341400X-RAY DIFFRACTION74.2
4.87-5.240.23881700.20271570X-RAY DIFFRACTION85.25
5.24-5.770.24671880.23611707X-RAY DIFFRACTION92.8
5.77-6.590.27782020.24911879X-RAY DIFFRACTION99.28
6.59-8.270.24262050.24261858X-RAY DIFFRACTION99.76
8.27-27.80.20931820.20891786X-RAY DIFFRACTION95.21

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